Abstract: The EXPLORER Consortium, through funding via a Transformative R01 and substantial commercial investment, has developed a 2-meter long total body PET scanner. This device has the potential to significantly alter the clinical application of PET through (a) substantial reduction in scan times, (b) substantial improvements in image quality, (c) substantial reduction in administered activity and (d) total-body coverage. This proposal aims to answer the basic questions that this new equipment raises with respect to the current clinical oncology application space: (1) how fast a scan can be performed to obtain standard diagnostic images using total-body PET; (2) whether breath-hold PET is feasible; (3) whether the scanner will support a 25-fold reduction in administered radiotracer activity; (4) whether there is value in delaying imaging to much later time-points after injection than current practice and (5) if the improvements in image quality obtained using standard injected doses and scan times have clinical utility. We will enroll 360 subjects from the clinical oncologic population seen at University of California, Davis; specifically, subjects affected by lung cancer, lymphoma and melanoma referred for PET/CT scan initial staging will be enrolled before starting treatment. We expect that the EXPLORER total-body PET scanner will be able to perform studies of similar diagnostic quality to conventional PET/CT scanners in approximately a minute or using a reduced dose corresponding to 1/25th of the standard dose. In addition we predict that breath-hold examinations will be feasible on EXPLORER. We also predict that very late time point imaging will be feasible on EXPLORER resulting in potential gains in lesion conspicuity. Finally, in collaboration with a team of highly-qualified team with expertise in oncology, radiation therapy, radiology and pathology, we will collect initial data to assess the added value of high-quality EXPLORER scans in oncologic imaging compared to conventional PET/CT scanners.